Hyperventilation in Differential Diagnosis WALTER I. rrUCKER, M.D.
of the occurrence of hyperventilation has not been sufficiently emphasized and, at time5, is not eonsidered in differential diagnosis. Of 100 consecutive cases at the Ilahey (jlinie in which the diagnosis was anxiety neurosis or anxiety hysteria, 60 patients had hyperventilation as a significant factor in the production of symptoms. In his excellent review, Rice 6 has reported that hyperventilation was a factor in the production of symptoms in 10.7 per cent of 1000 consecutive medical patients. Hyperventilation occurs clinically in association with acute hysterical episodes or with acute or chronic anxiety states, and actually a high percentage of neurotic patients displays some degree of hyperventilation. An increase in the depth and frequency of respirations is a part of the autonomic reaction of anxiety, and to this extent is an involuntary response. However, a feeling of tightness in the chest and throat and difficulty in getting an adequate breath, interpreted as a feeling of suffocation, frequently occur with anxiety. The patient may begin to breathe deeply and rapidly, more or less voluntarily, and to emit deep sighs or gasp for breath in a mistaken effort to overcome the feeling of suffocation. Often hyperventilation is initiated because of the widespread notion that taking deep breaths helps to relax the patient, and occasionally physicians suggest deep breathing for this purpose. Rice pointed out a more acute mode of onset with deep gasping as a reaction to acute pain or fright. Regardless of the mode of onset, symptoms are produced as a result of hyperventilation, increasing the anxiety and often progressing to a state of acute panic with fear of impending disaster or death. Tetany is rarely produced as the result of hyperventilation. It did occur in one patient who had a spontaneous attack at the clinic, with reduction of the blood calcium level to 8.7 mg. per 100 m!.; several weeks later it was 10.4 mg. per 100 m!. Many symptoms occur, however, before actual tetany is reached, and these symptoms can be grouped as follows: 1. Numbness and tingling of the extremities and face, and pains and stiffness of the extremities. These symptoms are thought to be the result of anoxia of the peripheral nerves. McDowa1l 5 has shown that with
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hyperventilation there is telnporary alkalosis from lowered carbon dioxide tension which lnay be 50 per cent of normal. He suggested that this results in a decreased rate of release of oxygen froln hemoglobin to the tissues. 2. Weakness, faintness, giddiness, buzzing in the head, blurring of vision, clouding of consciousness and syncope. These symptoms are considered to be caused by cerebral anoxia and are accompanied by slowing in the electroencephalographic tracing. Rubin and rrurner 7 have shown that the degree of electroencephalographic slowing and alteration of consciousness are influenced by the blood sugar level, being greater when it is relatively low. Gibbs et a1. 4 have shown that the slow waves that appear in the electroencephalogram with overventilation are caused by a drop in cerebral carbon dioxide and not by anemia secondary to cerebral vasoconstriction. They stated that in some supposedly healthy adults and in most persons with petit mal epilepsy, the cerebral vasoconstrictor response to low carbon dioxide tension is defective, this defect resulting in abnormal slowing of the electrical activity of the cortex during overventilation. 3. Tremulousness, sweating and fear. These symptoms can be readily accounted for by the accompanying anxiety. 4. Palpitation, chest pains and decreased blood pressure. Lowered carbon dioxide tension and alkalosis have been shown by Best and Taylor 1 to produce decreased cardiac output and increased pulse rate. Electrocardiographic changes in the fornl of lowering or inversion of the T waves have also been reported by Thompson. 9 Dale and Evans2 stated that low carbon dioxide tension affects the medullary centers and the blood pressure is reduced as a result, in part, of vasodilation in the splanchnic areas. Chest pain may be produced in two ways according to Rice: by pressure on the diaphragm of an overdistended stomach, and by muscular pain owing to the fatiguing exercise of hyperventilation. 5. Dryness of the mouth, belching, bloating, gas pains and dysphagia. Dryness of the mouth can readily be produced by overbreathing as a result of deficiency of saliva which may also have a bearing on the production of dysphagia. The other symptoms are thought to be produced by excessive air swallowing, a tendency which Rice found to be present in many cases of hyperventilation. Although some of these symptoms can be produced in anyone by voluntary deep hyperventilation, the severity of the symptoms produced varies in different individuals. Many persons displaying symptoms of anxiety and signs of sympathetic overactivity seem to be more susceptible to the effects of overbreathing. rfhis statement is based on observations of patients subjected to voluntary hyperventilation during office examination. Spontaneous episodes described by patients, however, are often much more severe and dramatic, probably because they occur in a setting of acute anxiety or hysterical states.
Hyperventilation in Differential Diagnosis
Enge13 has reported that tetany can be produced by epinephrine. 'I'his may be the reason that synlptoms from hyperventilation tend to develop more readily in anxious and hysterical patients than in other individuals. Sattler 8 has shown that symptolns arc associated with a rise of pH above 7.45, and this can be produced by hyperventilation. With such dramatic episodes, and with the possibility of producing so many different sylnptoms, frequently SOllle other organic condition is suggested, particularly when hyperventilation is not considered in the differential diagnosis. 'rhe case histories cited have been instructive to us, and illustrate SOllle of the conditions which lnay be simulated by the hyperventilation syndrome. CASE 1. A 15 year old girl had a head injury, followed by unconsciousness for five Ininutes, and residual symptoms of headaches and postural dizziness. Seven weeks later she began to have spells in which she heard ringing in the ears and then suddenly slumped into a chair or onto the floor. Occasionally, thrashing movenlents of the arms and legs occurred and she stated that at times she could not move for a few minutes although she was conscious of what was going on. l-'he local physician was treating her for epilepsy. l'he physical and neurologic examinations did not reveal abnormality. Hyperventilation produced a typical spell in which the patient slumped but did not fall, and recovered in ten seconds. The electroencephalogram was normal, and although she had two typical spells during hyperventilation, there was no change in the record. I t was later found there was a clash with one of the teachers in school. Her family had been greatly overconcerned and overprotective since the head injury. When these problems were better adjusted, and she was reassured, further episodes did not occur, although no medication was taken. Occasionally headache, dizziness and fatigue occurred. Diagnoses were made of post-traumatic syndrome, hysteria and hyperventilation syndrome.
Because of the association with hysterical episodes, and the occurrence of states of clouding of consciousness and syncope, attacks of hyperventilation often suggest epilepsy. Unlike Case 1, there may be definite slowing of the electroencephalogram on hyperventilation, and it may be difficult to establish the correct diagnosis. In the following case brain tumor was suspected. CASE 2. A 39 year old man had complained of spells of faintness for 18 months characterized by a warm flush, profuse sweating, pallor, blurred vision, faintness and paresthesias of the face. The attacks occurred often when he stooped over. On three occasions he had fainted for brief intervals. Originally, neurologic examination was reported as showing nysta~mus to right and upward gaze, weakness of the internal rectus muscle in the right eye, absent right ankle jerk and equivocal Babinski on the right. A roentgenogram of the skull showed calcification in the region of the internal carotid arteries and the electroencephalogranl was normal. Drain tumor was suspected and the patient was admitted to the hospital where the neurologic examination did not show any definite abnormalities. A left arteriograln and oxygen encephalogram gave negative results, although the latter did not show good filling. A ventriculogram was done because a third ventricle lesion was suspected, but was normal.
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It had been evident from the beginning that the patient had severe anxiety and many emotional problems. After the investigations Inentioned had been Inade, however, a history of overbreathing was obtained and the symptoms which he described as spells were reproduced by hyperventilation. He had no spells for four months after discharge from the hospital, during which time he took small amounts of phenobarbital.
With so many symptoms of hyperventilation referred to the cardiovascular system, some cardiac condition may well be suggested. 1'he follo,ving case simulated pheochromocytoma. CASE 3. A 58 year old woman was admitted to the hospital for study of paroxysmal hypertension. The blood pressure had fluctuated for 20 years, but in the last year and a half she had increasingly frequent attacks of abdominal and chest pain, palpitation, numbness, and severe pounding frontal and occipital headache. These attacks lasted from 24 to 48 hours and were accompanied by an increase in blood pressure up to 200 mm. systolic and 100 mm. diastolic from a previously normal range. Extensive studies were carried out, including histaminic tests for pheochromocytoma, electrocardiography, intravenous pyelography and pneumoencephalography, without any abnormality being found. Various medications were of no help. It was finally found that the spells, including the rise in blood pressure, could be brought on by hyperventilation. There was no abnormality in blood calcium or carbon dioxide levels during the episode. Not until after these studies were made was it found that the patient was severely anxious over her blood pressure, partly influenced by her local physician at the time of the beginning of her severe attacks. She had been loathe to engage in any sort of activity for fear of imminent death, and it was at times of particular fear over her condition that the attacks occurred.
Because of the chest pain, palpitation and breathing disorder accompanying hyperventilation the patient may often fear some cardiac disease, but organic disease can usually be ruled out by appropriate tests. .P aroxysmal tachycardia may be difficult to distinguish, particularly as it may occasionally be precipitated by emotional stress. CASE 4. A 23 year old WOlnan had a background of marked instability and irnInaturity. For two years she had had severe anxiety symptoms with anxiety attacks, many phobias and attacks of what she called "nervous hunger" when she was extremely anxious, had difficulty in getting her breath, was weak, tremulous, and noted paresthesias. She thought she had to eat sonlething at this time to prevent collapse, but the episodes were not regularly associated with fasting. A six-hour glucose tolerance test showed the lowest blood sugar level at 60 mg. per 100 ml. in the fourth hour. A spell occurred during the test but the patient was relieved after she was reassured by the physician. Later the symptoms were reproduced by 80 deep breaths. She had to be firmly and constantly directed to continue the deep breathing, as after only ten deep breaths she thought she could not continue. rrhe "spells" as described did not recur after the delnonstration of the connection with overbreathing and advice on avoiding hyperventilation. The anxiety attacks and other anxiety symptoms improved only gradually under treatment.
Hyperventilation in Differential Diagnosis
Because of the alleged relief by eating, hypoglycelnia had to be ruled out in this case. The electroencephalogram is nlore likely to show slow waves during hyperventilation in the presence of a relatively low blood sugar level, which may be a factor in the production of symptoms even though the blood sugar does not reach abnormally low levels. The report of relief of symptoms by eating or drinking is at times encountered and this may help largely by interrupting the breathing cycle. CASE 5. A 36 year old married woman had been bothered for many years by various gastrointestinal symptoms which had become progressively worse since the birth of her baby four years previously. She was particularly distressed by frequent episodes of vomiting and acute panic. She had developed fixed ideas that certain foods distressed her. She would first have gaseous distention and pain, then a feeling of suffocation leading to gasping for breath, associated with a feeling of acute anxiety, tremulousness, weakness and fear of impending disaster. She became nauseated and often. induced vOlniting by putting her finger in her throat, which gave some relief. Voluntary hyperventilation produced all the symptoms except gaseous distention and nausea. It became apparent that the patient swallowed air, became distended, and this, together with anxiety, led to hyperventilation which produced additional symptoms and resulted in acute panic. Induced vomiting often terminated the episode by interrupting hyperventilation.
Hyperventilation is not often mistaken for any organic gastrointestinal disease but, as in Case 5, it may be the key to the reasonable management of functional symptoms which could not be expected to respond to treatment directed toward controlling gastrointestinal symptoms. In many other instances hyperventilation may be the key to successful treatment and management even though it is not the prinlary disorder. In asthmatic attacks and particularly in intractable asthma associated with severe anxiety, hyperventilation is often a complicating factor, and the recognition and management of the tendency to overbreathe in such instances may be important in promoting recovery. The attacks of vertigo in Meniere's disease are sometimes associated with hyperventilation, or the reverse may occur-the reaction of hyperventilation may be mistaken for an attack of vertigo. The possibility that anxiety associated with hyperventilation should be kept in mind as a cause or a complicating factor in any condition characterized by sudden attacks of acute symptoms, particularly with difficulty in breathing. These case histories emphasize the importance of considering the hyperventilation syndrome in the differential diagnosis of various conditions. It is also important to emphasize the fact that hyperventilation occurs to some extent in a large percentage of acute anxiety and hysterical episodes. Most frequently, there are accompanying symptoms of emotional instability and phobias of disease, of going out alone, of crowds, or of closed spaces. When such symptoms are evident, the episode is more easily recognized as primarily a neurotic reaction.
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If the eondition is not eorrectly diagnosed, however, the patient's condition usually becomes worse because of uncertainty and secondary anxiety over the symptoms. l>hobias may well reach the point where they produce complete incapacity. If the condition is diagnosed, such secondary anxiety can be alleviated and the first step taken toward treating the emotional disorder. When hyperventilation is suspected as a part of the illness it has been found best first to 0 htain an accurate description of the "attacks" experienced. 1"'hen the patient can be directed to hyperventilate deeply and rapidly for at least one hundred times, without any previous explanation of the object thereof. It may require a great deal of urging and encouragement to persuade a severely unstable and hysterical patient to hyperventilate sufficiently, as the patient may become panicky or may cry when the first symptoms are produced. At times spontaneous hyperventilation may be precipitated and the patient may have difficulty resuming normal breathing even after being told to do so. After the completion of overbreathing, the patient is asked to describe the symptoms experienced, and finally asked whether the symptoms resemble the attacks of which he complains. When identical symptoms are produced, the patient will remember this experience, and he is ready to accept the fact that some or all of his symptoms can be produced by overbreathing. If at that time an explanation of the origin of symptoms and reassurance regarding the absence of some feared organic disease are given, the patient usually will be able to avoid hyperventilation when instructed to do so. Often after voluntary hyperventilation patients report that the symptoms produced are "like an attack coming on" but that all the symptoms they experience spontaneously are not present. Although sueh a report does not constitute proof that hyperventilation is an irnportant factor in the production of symptoms, it does suggest such a connection. If episodes of acute anxiety or hysteria could be reproduced, it seems likely that lnore severe and dramatic reactions to hyperventilation would be observed. Such reactions have been observed in sonle instances. Many physicians advise the patient to try to hold the breath or breathe into a paper bag to stop an attack of hyperventilation. rrhis may be satisfactory when the physician is present or the paper bag supplied, but such advice is usually impractical for the patient to follow on his own. It is better to help the patient to recognize what he is doing and then have him try to relax and to breathe normally. In patients who tend to hyperventilate frequently and chronically, ammonium chloride can be prescribed, and often seems to be of value clinically in lessening the severity of the symptoms produced. The suggestions made regarding treatment constitute the first stop toward dealing with the anxiety assoeiated with hyperventilation; sometimes no
Hyperventilation in Differential Diagnosis
other treatment is necessary, but if psychotherapy is required, rapport is facilitated by this approach. SUMMARY
Hyperventilation occurs frequently in association with acute anxiety or hysterical episodes. The symptoms of hyperventilation are listed. 'l-'hey are referred to the peripheral and central nervous systems, the cardiovascular system and the gastrointestinal system. Case histories are presented to illustrate simulation of symptoms of epilepsy, brain tumor, pheochromocytoma, hypoglycemia and gastrointestinal disorders. Suggestions are made regarding diagnosis and preliminary treatment. REFERENCES 1. Best, C. H. and rl"aylor, N. B.: The Physiological Basis of Medical Practice. Ed. 5, Baltimore, Williams & Wilkins Co., 1950. 2. Dale, H. H. and Evans, C. L.: Effects on the circulation of changes in the carbondioxide content of the blood. J. Physiol. 56: 125-145 (May) 1922. 3. Engel, F. L., Martin, S. P. and Taylor, H.: On relation of potassium to neurological manifestations of hypocalcemic tetany. Bull. Johns Hopkins Hosp. 84: 285301 (April) 1949. 4. Gibbs, E. L., Gibbs, F. A., Lennox, W. G. and Nims, L. F.: Regulation of cerebral carbon dioxide. Arch. Neurol. & Psychiat. 47: 879-889 (June) 1942. 5. McDowall, R. J. S.: 'fhe effect of carbon dioxide on the circulation. J. Physiol. 70: 301-315 (Oct.) 1930. 6. Rice, R. L.: Symptom patterns of the hyperventilation syndrome. Am. J. Med. 8: 691-700 (June) 1950. 7. Rubin, M. A. and Turner, E.: Blood sugar level and influence of hyperventilation on slow activity in the electro-encephalogram. Proc. Soc. Exper. BioI. & Med. 50: 270-272 (June) 1942. 8. Sattler, T. H., Marquardt, G. H. and Cummins. G. M., Jr.: Alkalosis due to hyperventilation; report of 3 cases. J.A.M.A. 146: 1125-1126 (July 21) 1951. 9. Thompson, W. P.: The electrocardiogram in the hyperventilation syndrome. Am. Heart J. 25: 372-390 (March) 1943.